Tyrosine decarboxylase (Tdc) belongs to an extensive group of aromatic amino acid decarboxylases (AADC) that are dependent on pyridoxal-5'-phosphate. AADCs have been well characterized in plants and animals (including vertebrates and invertebrates), and specific AADCs have been localized in the nervous systems of many animals. Within the vertebrate central nervous system a single AADC decarboxylates 5-hydroxytryptophan, L-dopa, tyrosine, phenylalanine, tryptophan, and tyramine, [56,57]; whereas, separate AADCs are responsible for the conversion of L-dopa to dopamine and of 5-hydroxytryptophan to 5-HT (dopa decarboxyase), and tyrosine to tyramine (tyrosine decarboxylase) in invertebrate nervous systems [45,58,59,60],
Figure 1. Schematic model of an insect OA neuron containing known and predicted proteins involved in OA biosynthesis. All locations are putative. Tdc, tyrosine decarboxylase; Tbh, tyramine beta-hydroxylase; Phe, phenylalanine; Tyr, tyrosine, Vit B6, vitamin B6; DHA, dehydroascorbic acid; Vit C, vitamin C; Cu++, copper; TA , tyramine. Transporters diagrammed as large circles represent plasma membrane, Na+ dependent antiporters; as triangles represent facilitative transporters; and as small circles represent ATP-dependent pumps. Open transporters have been described in insects whereas stippled transporters are speculative (see text).
The biochemical characterization of Tdc from locust brain extracts revealed two binding affinity components, suggesting that multiple forms Tdc may exist (Km, tyr0sine=1.31 and 50.8 ^M) . Recently, two Drosophila Tdc genes were identifified (dTdcl and dTdc2). DTdc2 encodes a 637 amino acid polypeptide with a predicted mass of 72,000 Da that is restricted to the insect nervous system and critical for octopamine synthesis . DTdc2 is 75% identical to other putative insect Tdcs (Anophiles gambiae and A. mellifera), 65% identical to mammalian AADCs, and 55% identical to plant AADCs. All AADCs contain a highly conserved pyridoxal-dependent domain characteristic of group II decarboxylases and studies of plant AADCs have revealed the role of pyridoxal 5'-phosphate in the decarboxlation reaction [61,62]. Direct experimental evidence has not confirmed the insect Tdc reaction mechanism, however, the conserved sequence homology among AADCs suggests that the catalytic mechanism is similar, if not also conserved. Pyridoxal 5'-phosphate first binds to AADCs via a Schiff base linkage with the e-amino group of a specific Lys residue. A transaldimination reaction follows in which the enzyme-pyridoxal-5'-phosphate Schiff base linkage is broken and a new Schiff base is formed between the substrate and pyridoxal-5'-phosphate. The substrate is then decarboxylated to form tyramine, and the enzyme and pyridoxal-5'-phosphate are regenerated. Thus, pyridoxal-5'-phosphate is vital for AADC and Tdc activity.
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